Early diagnosis is critical to the treatment of cancer and many other diseases. Today's diagnostic methods, however, often rely on the detection of individual and, in a few instances, small numbers of disease markers that have limited value in early diagnosis. Importantly, there is a growing body of evidence demonstrating that the diagnostic, prognostic, and stratification accuracy can be improved by detecting the presence of a large number of relevant biomarkers in serum samples. To this end, the creation of a platform capable of high throughput and high detection sensitivity stands as a vital first step. Such a platform must also handle samples of preciously limited volume and meet the demand for ever shorter turn-around-times. These same attributes are at the heart of advances in the discovery and screening of new disease markers. This multidisciplinary project at the University of Utah seeks to create a new nanotechnology-based platform - the multiplexed magnetoresistive immunoassay (mMRIA) system - for the early detection of cancer. It targets pancreatic cancer as the first step in platform development and performance validation. Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States. The 5-year survival rate of ~4%, the lowest of any cancer, underscores the importance of the project. Project goals include: (1) strategies to markedly enhance magnetoresistive sensor performance (e.g., noise and signal attributes, internal response calibration, design and layout of the addresses on the capture substrate array, separation between sensor (i.e., reader) and scanned array, and analytical descriptors of signal transduction);(2) synthesis of novel magnetic nanoparticles to serve as labels with a strong magnetic signature;(3) integration of advances in hydrodynamics to increase sample and label flux to the solid phase array as a means to reduce TAT and simultaneously lower the background signal;and (4) design and construction of instrumentation to quantitatively read thousands of immunoassay addresses in less than one minute. RELEVANCE (See instructions): This project is focused on the development of a nanotechnology-based platform for the early diagnosis of cancer. The goal is to construct and test this technology, which is based on the magnetics concepts that read the hard disk drive in most of today's laptop computers and portable music media players, that will simultaneously and rapidly detect large numbers of disease markers at unprecedented levels of sensitivity.